The cell biology of secretory pathways has evolved into an exciting but complex field that provides insight into a staggering array of human diseases including Alzheimer's, drug addiction, autism, diabetes, obesity, and various cancers. Initially, this GRC provided much emphasis on processing enzymes - those that catalyze the maturation of hundreds of bioactive peptides, but in addition membrane-associated proteolytic systems, particularly the matrix metalloproteases and the secretases, that control tissue remodeling and membrane shedding in normal cells, as well as the extracellular activation and/or inactivation of a variety of molecules such as growth factors and anti-microbial peptides. The focus has expanded to a cell biological perspective, including the regulation of protein sorting and traffic, vesicle formation and the formation of dense-core secretory granules in stimulus-coupled endocrine and neuroendocrine cells. The cooperative roles of the secretory pathway and other protease systems, taken in the context of the underlying cellular trafficking machinery that contributes to complex, prevalent diseases, provide urgent reasons to continue this multi- disciplinary approach to examine the interactions of secretory pathway components in homeostasis and in disease. The Protein Processing, Trafficking and Secretion Gordon Research Conference are unique in convening scientists from many biological disciplines to join in a forum for just this purpose. This recurring Conference has remained innovative because it works to identify the most exciting and fundamental questions. In large part, this involves developments in the study of pathophysiological states that affect secretory pathways: A notable example is the potential clinical significance of PCSK9 to help control serum cholesterol levels. PCSK9 belongs to a small processing enzyme family that has been extensively studied by this GRC over the years, and drugs for which are now entering the public sphere with considerable anticipation. Likewise, the 2016 Program will present further novelty by featuring increased emphasis on the mechanisms underlying endocytosis and exocytosis. This emphasis jibes with renewed interest by neurobiologists and endocrinologists in the cell biology underlying release of bioactive peptides and peptide hormones. The Program is organized by a diverse committee that represents Academic, Industrial and Governmental science. The GRC is associated with a GRS (Gordon Research Seminar) that is specially designed for young trainees and which has enjoyed success as a scientific and mentoring adjunct. The support we request will permit participation in the GRS and GRC by trainees and junior stage colleagues.